Dosage of baloxavir marboxil for pediatric patients

Abstract

The present invention relates to a method for treating an influenza virus infection, wherein said method comprises administering an effective amount of a compound to a patient having an influenza virus infection, wherein the compound has one of the formulae (I) and (II), as set forth herein, or is a pharmaceutically acceptable salt thereof, and wherein dosages set forth herein are used.

1 . A method for treating an influenza virus infection, wherein said method comprises administering an effective amount of a compound to a patient having an influenza virus infection, wherein the compound has one of the following formulae (I) and (II): 
       
         
           
           
               
               
           
         
         or is a pharmaceutically acceptable salt thereof, 
         and wherein the following dosage is used: 
         (i) in a patient that is younger than 1 year:
 (a) if the patient is younger than 4 weeks, then the effective amount is 0.8-1.2 mg/kg body weight, preferably about 1 mg/kg body weight; 
 (b) if the patient is 4 weeks or older but younger than 3 months, then the effective amount is 0.8-1.2 mg/kg body weight, preferably about 1 mg/kg body weight; 
 (c) if the patient is 3 months or older but younger than 12 months, then the effective amount is 1.8-2.2 mg/kg body weight, preferably about 2 mg/kg body weight; 
 
         (ii) in a patient that is 1 year or older but younger than 12 years:
 (a) if the patient has a body weight of less than 20 kg, then the effective amount is 1.8-2.2 mg/kg body weight, preferably about 2 mg/kg body weight; or 
 (b) if the patient has a body weight of 20 kg or more, then the effective amount is 35-45 mg, preferably about 40 mg. 
 
       
     
     
         2 . The method of  claim 1 , wherein the patient is white. 
     
     
         3 . The method of  claim 1 , wherein the patient does not have an Asian ethnicity. 
     
     
         4 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered in the form of a suspension of granules. 
     
     
         5 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is orally administered. 
     
     
         6 . The method of  claim 1 , wherein the patient is 1 year old or older but younger than 5 years. 
     
     
         7 . The method of  claim 1 , wherein the patient is 5 years old or older but younger than 12 years. 
     
     
         8 . The method of  claim 1 , wherein the patient has a body weight which is less than 40 kg. 
     
     
         9 . The method of  claim 1 , wherein the patient is healthy except for the influenza virus infection. 
     
     
         10 . The method of  claim 1 , wherein the patient is diagnosed as having an influenza virus infection:
 (a) due to the presence of fever of 38° C. or more (tympanic temperature); and at least one respiratory symptom, preferably cough and/or nasal congestion; and/or   (b) by using an influenza test kit.   
     
     
         11 . The method of  claim 1 , wherein the influenza virus is a type A influenza virus. 
     
     
         12 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered within 96 hours from the time of symptom onset, preferably within 48 hours from the time of symptom onset. 
     
     
         13 . The method of  claim 12 , wherein the symptom onset is the time point of the onset of at least one systemic symptom and/or at least one respiratory symptom. 
     
     
         14 . The method of  claim 13 , wherein the at least one systemic symptom is selected from the list consisting of headache, feverishness, chills, muscular pain, joint pain, and fatigue. 
     
     
         15 . The method of  claim 13 , wherein the at least one respiratory symptom is selected from the list consisting of coughing, sore throat, and nasal congestion. 
     
     
         16 . The method of  claim 1 , wherein the treated patient to whom the compound, or a pharmaceutically acceptable salt thereof, has been administered has a decreased virological activity as compared to an untreated patient to whom the compound, or a pharmaceutically acceptable salt thereof, has not been administered. 
     
     
         17 . The method of  claim 16 , wherein the virological activity is measured by:
 (i) determination of the time to cessation of viral shedding;   (ii) determination of the influenza virus titer; and/or   (iii) determination the amount of virus RNA.   
     
     
         18 . The method of  claim 17 , wherein the duration of influenza virus shedding is measured as time to shedding cassation following symptom onset. 
     
     
         19 . The method of  claim 17 , wherein the amount of virus RNA is measured by using reverse transcriptase-polymerase chain reaction (RT-PCR). 
     
     
         20 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, reduces the time to alleviation of influenza signs and symptoms (TASS) by at least 6 hours, preferably by at least about 12 hours as compared to an untreated patient to whom the compound or a pharmaceutically acceptable salt thereof, has not been administered. 
     
     
         21 . The method of  claim 1 , wherein the time from diagnosis of the influenza virus infection until recovery is decreased in the treated patient to whom the compound, or a pharmaceutically acceptable salt thereof, has been administered as compared to an untreated patient to whom the compound, or a pharmaceutically acceptable salt thereof, has not been administered. 
     
     
         22 . The method of  claim 1 , wherein the patient has recovered when at least one of the following recovery criteria is met and remains met for at least 21.5 hours:
 (i) return to afebrile state (tympanic temperature≤37.2° C.);   (ii) a score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms as specified in items 14 and 15 of the Canadian Acute Respiratory Illness and Flu Scale (CARIFS), preferably a score of 0 (no problem) or 1 (minor problem) for all 18 symptoms specified in the (CARIFS);   (iii) cessation of viral shedding; and/or   (iv) return to normal health and activity.   
     
     
         23 . The method of  claim 22 , wherein return to normal health and activity is achieved if the patient is able to return to day care or school, and/or to resume his or her normal daily activity in the same way as performed prior to developing the influenza virus infection. 
     
     
         24 . The method of  claim 16 , wherein the untreated patient has been administered with oseltamivir. 
     
     
         25 . The method of  claim 1 , wherein the administration of the compound, or a pharmaceutically acceptable salt thereof, prevents the occurrence of an influenza-related complication. 
     
     
         26 . The method of  claim 25 , wherein the influenza-related complication is at least one of the complications selected from the group consisting of radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, and myositis. 
     
     
         27 . The method of  claim 1 , wherein death of the patient caused by the influenza virus infection is prevented by the administration of the compound, or a pharmaceutically acceptable salt thereof. 
     
     
         28 . The method  claim 1 , wherein the requirement of antibiotics is prevented by the administration of the compound, or a pharmaceutically acceptable salt thereof. 
     
     
         29 . The method of  claim 1 , wherein the compound has the formula (I), or a pharmaceutically acceptable salt thereof.